Evolution and function of mesoscale protein assemblies

Mutations and changes in a protein's environment are well known for their potential to induce misfolding and aggregation, including amyloid formation. Alternatively, such perturbations can trigger new interactions that lead to the polymerization of folded proteins. In contrast to aggregation, this process does not require misfolding and, to highlight this difference, we refer to it as agglomeration. This term encompasses the amorphous assembly of folded proteins as well as the polymerization in one, two, or three dimensions. Proteins show a remarkable potential to agglomerate even by single surface point mutations. This movie illustrates this point: a single point mutation triggers a normally soluble protein to form large fibers (Garcia Seisdedos et al. Nature, 2017)

We are now investigating the impact of such aberrant assemblies on cellular functions, and also examining general functional properties of natural agglomerates.